SUMMARY The adipocyte-derived hormone adiponectin promotes metabolic and cardiovascular health. Circulating adiponectin increases in lean states such as caloric restriction (CR), but the reasons for this paradox remain unclear. Unlike white adipose tissue (WAT), bone marrow adipose tissue (MAT) increases during CR, and both MAT and serum adiponectin increase in many other clinical conditions. Thus, we investigated if MAT contributes to circulating adiponectin. We find that adiponectin secretion is greater from MAT than from WAT. Notably, specific inhibition of MAT formation in mice results in decreased circulating adiponectin during CR, despite unaltered adiponectin expression in WAT. Inhibiting MAT formation also alters skeletal muscle adaptation to CR, suggesting that MAT exerts systemic effects. Finally, we reveal that both MAT and serum adiponectin increase during cancer therapy in humans. These observations identify MAT as an endocrine organ that contributes significantly to increased serum adiponectin during CR, and perhaps in other adverse states.

Maturity-onset diabetes of the young, or MODY-monogenic diabetes, is a not-so-rare collection of inherited disorders of non-autoimmune diabetes mellitus that remains insufficiently diagnosed despite increasing awareness. These diagnoses are important to efficiently and accurately diagnose, given the clinical implications of syndromic features, cost-effective treatment regimen and the potential impact on multiple family members. Proper recognition of the clinical manifestations, family history, and cost-effective lab and genetic testing provide the diagnosis. All patients must undergo a thorough history, physical examination, multi-generation family history, lab evaluation (HbA1c, glutamic acid decarboxylase antibodies (GADA), islet antigen 2 antibodies (IA-2A), and Zinc Transporter 8 antibodies (ZnT8)). The presence of clinical features with 3 (or more) negative antibodies is indicative of MODY-monogenic diabetes, and is followed by genetic testing. Molecular genetic testing should be performed before attempting specific treatments in most cases. Additional testing that is helpful in determining the risk of MODY-monogenic diabetes is the MODY clinical risk calculator (> 25% PPV suggestive of MODY) and 2-hour post-prandial (after largest meal of day) urinary C-peptide to creatinine ratio (with a > 0.2 nmol/mmol to distinguish HNF1A- or 4A-MODY from Type 1 Diabetes) 1,2. Treatment, as well monitoring for microvascular and macrovascular complications is determined by the specific variant that is identified. In addition to the diagnostic approach, this article will highlight recent therapeutic advancements when patients no longer respond to first line therapy (historically sulfonylurea treatment in many variants).

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Context Preoperative imaging is performed routinely to guide surgical management in primary hyperparathyroidism, but the optimal imaging modalities are debated. Objective Our objectives were to evaluate which imaging modalities are associated with improved cure rate and higher concordance rates with intraoperative findings. A secondary aim was to determine whether additive imaging is associated with higher cure rate. Design, Setting, and Patients This is a retrospective cohort review of 1,485 adult patients during a 14-year period (2004-2017) at an academic tertiary referral center that presented for initial parathyroidectomy for de novo primary hyperparathyroidism. Main Outcome Measures Surgical cure rate, concordance of imaging with operative findings, and imaging performance. Results The overall cure rate was 94.1% (95% CI 0.93-0.95). Cure rate was significantly improved if sestamibi/SPECT was concordant with operative findings (95.9% vs. 92.5%, p = 0.010). Adding a third imaging modality did not improve cure rate (1 imaging type 91.8% vs. 2 imaging types 94.4% vs. 3 imaging types 87.2%, p = 0.59). Despite having a low number of cases (n=28), 4-D CT scan outperformed (higher sensitivity, specificity, PPV, NPV) all imaging modalities in multi-glandular disease and double adenomas, and sestamibi/SPECT in single adenomas. Conclusions Preoperative ultrasound combined with sestamibi/SPECT were associated with the highest cure and concordance rates. If pathology was not found on ultrasound and sestamibi/SPECT, additional imaging did not improve the cure rate or concordance. 4-D CT scan outperformed all imaging modalities in multiglandular disease and double adenomas, and sestamibi/SPECT in single adenomas, but these findings were underpowered.

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In this review, we have highlighted work that has clearly demonstrated that mitogen-activated protein kinase (MAPK) phosphatase-1 (MKP-1), a negative regulator of MAPKs, is an important signaling mediator in bone, muscle, and fat tissue homeostasis and differentiation. Further, we examined recent studies with particular focus on MKP-1 overexpression or deletion and its impact on tissues connected to bone. We also summarized regulation of MKP-1 by known skeletal regulators like parathyroid hormone (PTH)/PTH-related peptide (PTHrP) and bone morphogenic proteins. MKP-1's integration into the pathophysiological state of osteoporosis, osteoarthritis, rheumatoid arthritis, obesity, and muscular dystrophy are examined to emphasize possible involvement of MKP-1 both at the molecular level and in disease complications such as sarcopenia- or diabetes-related osteoporosis. We predict that understanding the mechanism of MKP-1-mediated signaling in bone-muscle-fat crosstalk will be a key in coordinating their activities and developing therapeutics to improve clinical outcomes for diseases associated with advanced age.